Virtually safe dose level

Virtually safe dose (VSD) The dose of chemical corresponding to the level of risk determined and accepted by regulatory agencies the dose-to-risk relationship is based on a chemical dose-response curve. 

States Environmental Protection Agency, realizing that small amounts of dioxins are found ubiquitously (especially in food), has established a virtually safe dose for these chemicals. This dose is the dioxin level that is assumed to cause cancer in only one out of one million exposed persons. The caveat to the latter is that dose results from an upper bound estimate of cancer potency and the probability of cancer for the exposed population may be far less, or, in fact, zero. 

The European Union (Commission Directive 93/67/EEC, Article 3, paragraph 1 repealed) and WHO (1994) have used the NOAEL/uncertainty factor approach for nongenotoxic carcinogens that are believed to have an effect threshold (WHO 1994). Eor genotoxic carcinogens, however, the regulatory default is applied that is based on the assumption that if one hit could cause a mutation and eventually result in cancer, then any exposure level could be associated with a finite cancer probability. Under such circumstances, a mathematical model (that quantitatively describes the relation between dose [exposure] and cancer [probability]) would be required to determine a virtually safe dose (VSD), a dose associated with an insignificantly small cancer risk. The choice of the model has an impact on risk predictions, because it usually involves extrapolation to low doses for which no data may be available, and has remained controversial. 

The high to low dose extrapolation problem is conceptually straight-forward. The probability of a toxic response is modeled by a dose-response function P(D) which represents the probability of a toxic response when exposed to D units of the toxic agent. A general mathematical model is chosen to describe this functional relationship, its unknown parameters are estimated from the available data, and this estimated dose-response function P(D) is then used to either (1) estimate the response measure at a particular low dose level of interest or (2) estimate that dose level corresponding to a desired low level of response (this dose estimate is commonly known as the virtually safe dose, VSD). 

Table VI. Virtually Safe Doses (VSD) for 2-AAF Based Multistage and Log Normal Models Applied To Different Dose Level Combinations...

If a compound gives a carcinogenic response in the bioassay, the multistage model is used to determine the level of insignificant risk which is considered to be 1 in 1 million (4). The mathematically derived value is called the Sq or virtually safe dose. The Sq value is multiplied by consumption factors as described above after it is multiplied by 3 to convert the value to the meat portion of man s diet... 

This question of whether it is scientifically valid to derive the lifetime control limit by using threshold or non-threshold models defines what cleanup levels are proposed for a site. The action level proposed by CDC for residential soil in Missouri is 1 ppb, based on a series of exposure assumptions and on virtually safe doses for 10"° cancer risk of 0.0276 pg/kg/day (U). If one assumes a different threshold - based model, as did Dutch, Swiss, German, and Canadian workers (9), one obtains maximum allowable daily intake of 1-10 pg/kg/day. If one uses the same exposure calculations as CDC, one could then accept 4-40 ppb in residential soil according to these allowable daily intakes. CDC and ERA have allowed 7 ppb as acceptable residual concentrations at an industrial site in New Jersey (IJ). At Seveso, cleanup levels were set at 45 ppt for nonagricultural soil and 7 ppt for agricultural soil... 

Figure 4 Both the fit of the multistage model to the Kociba et al (1978) experimental data on hepatocellular neoplastic nodule or carcinoma in female rats and the corresponding estimate of the virtually safe dose (VSD) are dominated by the higher experimental dose levels and are ESSENTIALLY UNAFFECTED by the results obtained at lower doses (From ref. 76). Reproduced with permission from Paustenbach et al. Copyright 1986, Academic Press.

In order to conduct a risk assessment, a suitable risk model and toxicology data base must be selected. With these a dose corresponding to an acceptable level of risk may be calculated. This dose is usually referred to as the Virtually Safe Dose (VSD)... 

The acceptable daily intake should not be ignored in situations involving carcinogens. It is conceivable that for a product used only a few days a year that the permissible exposure level calculated from the virtually safe dose could be greater than that calculated from the ADI. Therefore, these values should be compared and the lower value adopted. 

HypervitaminosisC. The vitamin is considered very safe. At one time, many of the over-the-counter products contained significant amounts of sodium ascorbate, which would be contraindicated in people on low sodium diets. Today s products are virtually sodium free unless labeled otherwise. Nevertheless, there are intermittent reports of adverse reactions associated with high doses. Therefore, there are Tolerable Upper Intake Levels, but these are very high relative to the RDAs. The UL to RDA ratio averages about 20. 

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